BIOLOGICAL TREATMENT FOR UNIPOLAR DEPRESSIONANTIDEPRESSANT DRUGS

BIOLOGICAL TREATMENTS FOR DEPRESSION

The Unit 2 Exam expects you to know about one biological treatment for a disorder other than schizophrenia; this page considers unipolar depression. and drug therapy (also known as pharmacotherapy or chemotherapy).

The first antidepressant drug was isoniazid, which was developed as a cure for tuberculosis. It had the side-effect of sending the patients into states of euphoria (pleasure).

In the 1950s, it was discovered that isoniazid and other hydrazines worked by blocking brain enzymes called monoamine oxidases (MAO). These enzymes were responsible for controlling the amount of monoamines in the brain - neurotransmitters like serotonin, noradrenaline and dopamine. When MAOs were inhibited, the level of monoamines increased and this caused an improvement in mood. If MAOs were inhibited too much, the patients went from being cheerful, alert and sociable to showing aggressive or psychotic symptoms, which the researchers called "dancing in the hall".

This led to the creation of the first antidepressant drugs, which were monoamine oxidase inhibitors (MAOI). These drugs are particularly strong and today they are usually used as a "last resort" for patients who are resistant to other antidepressants. This is because they can cause irreversible high blood pressure.

The second generation of antidepressant drugs were tricyclic antidepressants, which were originally tested on patients with schizophrenia. Tricyclics like Elavil became popular in the '60s. Although they don't work by inhibiting MAO, they still have the effect of boosting serotonin and noradrenaline activity. They aren't as dangerous as MAOIs but they still have unpleasant side-effects (constipation, blurred vision, memory loss) and it's possible to overdose, leading to psychosis and coma.

Theses drugs provided relief to 60-80% of patients, but they also carried serious side effects, caused withdrawal symptoms when people tried to stop taking them and caused the occasional death from overdose.

These antidepressants had been discovered accidentally, but now that researchers understood how they worked, new antidepressants were developed to produce the same effects without the side-effects. These "third generation" drugs were developed in the 1980s and '90s and worked by preventing the reuptake of serotonin in particular, boosting the amount of serotonin active in the synapses but leaving other neurotransmitters like dopamine unaffected. These are known as selective serotonin reuptake inhibitors (SSRI). The most famous brand of SSRI is Prozac which became the most-prescribed antidepressant in America by the 1990s.

A one-and-a-half minute summary of SSRIs

SSRIs have fewer side-effects than the earlier antidepressants, but there are still adverse reactions, like headaches, weight gain, lethargy, nausea and sexual problems.

SSNI drugs followed, which prevent the reuptake of noradrenaline (norepinephrine) and leave the other neurotransmitters unaffected. SSNIs are also effective for people with anxiety disorders or obsessive compulsive disorder (OCD). They have similar side-effects to SSRIs.

Top 10 side-effects of antidepressants. "Suicidal ideation" means compulsive thoughts about suicide. Notice that, for some people, depression is a side-effect of antidepressants, which is a cruel irony.

In this 5-minute video, Julie sums up the biological explanation ﻿and ﻿how antidepressants work - including neurogenesis and the importance of the hippocampus

APPLYING BIOLOGICAL TREATMENTS FOR DEPRESSIONAO2

Which antidepressant should be prescribed is based on the client's medical history and the previous medication they have tried. MAOIs and tricyclics react badly together and shouldn't be taken within 2 weeks of each other. About 30% of patients fail to respond to any particular drug or show only faint benefits. However, clients who do not respond to one drug, often respond to a different one, therefore "trial-and-error" is needed.

The National Institute for Health and Care Excellence (NICE, 2014) guidance recommends SSRI as the "first choice" antidepressant. a different SSRI may be tried if the client doesn't respond to the first. If that does not work, doctors can prescribe tricyclics or MOAIs.

Today's advice is not to offer people more than one antidepressant drug at a time, because that reduces the risk of side-effects.

THE COURSE OF TREATMENT

It may take 3 weeks, before antidepressants take effect. People with depression often take antidepressants for 6-12 months but, even though their symptoms have gone, if they stop taking the drugs too soon, the symptoms may return.

At least 30% the people diagnosed with depression don’t take their drugs as recommended. Many people don’t like the idea of taking drugs every day, or forget to take them, or decide they don’t need the drugs any more because they feel well.

People also stop taking their antidepressants because of the side effects. Even if people don't experience dizziness, drowsiness or weight gain, many report that the antidepressants remove their negative feelings but leave them not caring about anything. They would prefer to come off the pills in order to feel again, even if the feelings are unhappy ones.

20% of people who come off antidepressants experience discontinuation symptoms like anxiety, mood swings, flu symptoms or tremors. These aren't "withdrawal" symptoms, because antidepressants aren't addictive like caffeine or cigarettes. Instead, your body has to adjust to a sudden change in brain chemistry. Discontinuation symptoms are less likely with drugs like Prozac that take a long time to clear out of the body.

Prozac Nation was a 1994 bestseller in which Elizabeth Wurtzel describes her battle with depression. It was made into a film in 2001 with Christina Ricci playing Wurtzel. It doesn't pull any punches - and Wurtzel is a less-than-likeable character - but Ricci is fantastic and it gives an insight into the experience of unipolar depression and life on antidepressants.

EVALUATING BIOLOGICAL TREATMENTSAO3

Credibility

Drug therapy represented a major advanced when it was introduced in the 1950s. Antidepressants are more effective and more ethical than the shock therapy that had been in use before. New research goes on to improve antidepressants, so that they have fewer side-effects than the old MAOIs and tricyclics.

Drug therapy is supported by the Monoamine Hypothesis and lends support to the biological explanation of depression. All major antidepressants affect neurotransmitters in the brain to bring about changes in symptoms. When an idea is backed up by a well-researched scientific theory, it has construct validity.

Some critics argue that antidepressants are a "placebo" - they only work because the patient believes they will work. This was tested by Kirsch et al (2008) who reviewed 47 trials of patients with mild or severe depression who were prescribed SSRI antidepressants or a placebo (sugar pill) that looked like an antidepressant. The patients with severe depression did show a statistically greater response to antidepressants than to placebos. This suggests that antidepressants do work - but that a lot of their effectiveness can be explained by the Placebo Effect because patients feel better if they believe in the treatment they are getting (even if it doesn't do anything).

Objections

Drug therapy doesn't work for everyone. Although more patients respond to the SSRIs than to the first generation antidepressants, this is still not all patients. It is estimated only 70% of patients benefit from drug treatments.

All the drugs used to treat depression have adverse reactions; these could include weight gain, nausea and drowsiness. Some people feel the side-effects are worse than the symptoms they are alleviating. The Recovery Model takes a different approach, urging people with depression to stop taking drugs and find different ways of living with their symptoms.

The Recovery Movement makes some good points but also advocates a lot of conspiracy theories, like the idea that the medical drugs companies ("Big Pharma") deliberately push medication onto people to boost their own profits.

Nonetheless, there is a growing concern that antidepressants are being over-prescribed. The study by Kirsch et al. (2008) caused a stir by showing that SSRIs weren't any better than placebos when it came to mild depression. This would mean doctors were prescribing pills that carried side-effects but weren't doing mildly depressed patients any good (and perhaps weren't doing severely depressed patients enough good to justify the side-effects).

while many people may benefit from antidepressant treatment (although most of them to a degree that is not clinically significant), about 1 in 4 are made worse - Irving Kirsch

In the UK, over 40 million antidepressants are prescribed every year and, in the United States, 1 person in 10 has been prescribed antidepressants and 1 in 6 of those taking antidepressants aren't depressed or sufffering from any mental disorder This is partly due to the huge popularity of Prozac, which acquired a reputation as a "happiness pill" that could improve the quality of life for people with normal moods as well as people with mood disorders.

This links to concerns about the medicalisation of normal experience - ordinary people are turning to powerful drugs to help them cope with life's ordinary ups and downs.

The great advantage of CBT over drug therapy is the lack of side-effects. On the other hand, cognitive therapy can be more threatening for some patients, because you have to open up and talk about your problems. For some people, popping a pill is preferable to sharing unpleasant thoughts and feelings with a therapist.

Both treatments take time to be effective: drug therapy takes weeks, cognitive therapy takes months. This means a patient who is very distressed and perhaps suicidal will get much more help in the short term from antidepressants.

However, in the long term, CBT might be more beneficial. Treatments can either cure the disorder or suppress the symptoms without changing the underlying problem (palliative treatments). Drug therapy for unipolar depression is palliative rather than curative, which is why there are high relapse rates when the drugs are stopped. CBT is curative instead.

Hollon et al. (2005) studied patients who received treatment for 16 weeks then were observed for 12 months to see if their symptoms returned (relapse). There were 3 groups: (1) patients who received CBT; (2) patients who received drug therapy; and (3) patients received drug therapy which continued over the 12 month observation period. Only 31% of CBT patients suffered a relapse compared to 76% of those treated with drugs and 47% of the patients who carried on taking antidepressants. These findings show that drug therapy is only palliative whereas cognitive therapy offers a better cure.

The NHS recommends an "integrated approach" involves combining the two treatments. Antidepressants might give some patients the confidence and concentration to take part in CBT. It may be possible to reduce the dependency on antidepressants as the cognitive therapy takes effect.

Applications

Antidepressants have long been established as a relatively cheap, effective treatment, which quickly reduce symptoms and enable many people to live relatively normal lives. Relapse is likely when patients stop taking the drugs. Drug treatment is usually superior to no treatment at all. Around 70% of patients benefit from drug treatments.

One of the big positives of drug therapy is that it requires very little effort from the client; they just have to take some pills. However, this is not always true as most doctors use drug therapy alongside another treatment, like counseling or family therapy. This is an "integrated approach".

However, there's a risk that patients stop taking their medication. They may do this because they don't understand their illness, because their relationship with their clinician isn't very good or because they don't like the side-effects.

Researchers like Irving Kirsch argue that antidepressants are really placebos and do little good for all but the most severely depressed patients. If Kirsch is right, we should cut down the amount of antidepressants we prescribe and focus more on counseling and cognitive therapies.

EXEMPLAR ESSAYHow to write a 8-mark answer

Using your knowledge of a disorder other than schizophrenia, assess how effective a biological treatment would be compared to a psychological treatment. (8 marks)

A 8-mark “evaluate” question awards 4 marks for describing biological treatments for depression (AO1) and 4 marks for evaluating them, including a comparison with CBT (AO2). You need a conclusion to get a mark in the top band (7-8 marks).

DescriptionBiological treatments for depression involve antidepressant drugs. Examples are MAOIs, tricyclics and SSRIs.These drugs work by changing the brain's chemistry, especially monoamines like serotonin and noradrenaline.SSRIs like Prozac work by preventing the reuptake of serotonin in the synapse. They are the "third generation" of antipsychotics developed in the '80s and '90s.Antidepressants tend to take 3 weeks to take effect and a course lasts 6-12 months. A cognitive therapy might last a year and take months to show any benefits.

EvaluationAntidepressants have side-effects, which CBT doesn't. However, new SSRIs have fewer side-effects than the old MAOIs.Antidepressants may be placebos. Irving Kirch showed that, for mild depression, SSRIs had no more effect than a placebo pill.Even when antidepressants do work, they are palliative, not curative. This means they only cancel out the symptoms but don't cure the problem.Hollon et al. compared antidepressants with CBT and found, a year later, only 36% of CBT patients had relapsed compared to 76% of the patients who took antidepressants. This shows CBT is superior.

ConclusionThere are concerns that we are over-prescribing antidepressants, perhaps to people on whom they have no effect. CBT would be a better form of treatment for mild or moderate depression.

Notice that for a 8-mark answer you don’t have to include everything about the treating depression. You will notice I haven't mentioned monoamine oxidase or the problems of discontinuation or offered specific side-effects. But it is a balanced answer - one half description and one half evaluation.